This chapter focuses on recently emergent paramyxoviruses that are associated with zoonotic disease, Hendra virus (HeV), Nipah virus (NiV), and Menangle virus (MeV). Molecular biological studies have made substantial contributions to the characterization of recently emergent zoonotic paramyxoviruses. As for other paramyxoviruses, the NiV surface glycoproteins are the primary targets for neutralizing antibodies. The conservation of most of the structurally important amino acids suggests that the attachment proteins of HeV and NiV would have structures that are very similar to the structure proposed for the attachment proteins of other paramyxoviruses. The development or characterization of animal models to study henipavirus infections is critical for understanding their pathogenesis and for development of therapeutics or vaccines. The chapter describes the pathogenesis and immune responses of human infections for each virus. Traditional techniques of virus isolation in cell culture, electron microscopy, enzyme-linked immunosorbent assay-based serology, neutralization assays, and immunohistochemical (IHC) techniques have been employed in the diagnosis of the zoonotic paramyxoviruses. NiV and HeV are internationally classified as biosafety level or biosecurity level 4 (BSL-4) agents; thus, clinical specimens suspected to be infected with these agents must be handled with caution. Pig farmers in areas in which NiV may be endemic should be educated regarding the features of Nipah encephalitis in pigs and to report any unusual disease. Since transmission is possible without close contact with pigs, exposure to potentially infected animals should be completely avoided, if possible. Persons handling pigs or their excreta should wear protective equipment such as gloves and masks.

Schematic representation of the genomes of viruses in the subfamily Paramyxovirinae. Genomes are single-stranded, negative-sense RNA shown in the 3′-to-5′ (left-to-right) orientation. Gray boxes indicate protein coding regions, and solid lines indicate noncoding regions. Numbers under the protein coding regions on the henipavirus genome indicate the percent amino acid identity between HeV and NiV for the indicated protein. Abbreviations for the structural genes are as follows: N, nucleoprotein; P, phosphoprotein; M, matrix protein; F, fusion protein; A, attachment protein; H, hemagglutinin protein; HN, hemagglutinin-neuraminidase; L, polymerase. The schematic genome for rubulaviruses is that of mumps virus and shows the position of the gene for the small hydrophobic protein (SH).

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FIGURE 2

Schematic representation of the genomes of viruses in the subfamily Paramyxovirinae. Genomes are single-stranded, negative-sense RNA shown in the 3′-to-5′ (left-to-right) orientation. Gray boxes indicate protein coding regions, and solid lines indicate noncoding regions. Numbers under the protein coding regions on the henipavirus genome indicate the percent amino acid identity between HeV and NiV for the indicated protein. Abbreviations for the structural genes are as follows: N, nucleoprotein; P, phosphoprotein; M, matrix protein; F, fusion protein; A, attachment protein; H, hemagglutinin protein; HN, hemagglutinin-neuraminidase; L, polymerase. The schematic genome for rubulaviruses is that of mumps virus and shows the position of the gene for the small hydrophobic protein (SH).

Schematic representation of the coding strategy found in the P protein gene of NiV. The predicted P protein mRNA is 2,704 nucleotides in length (nucleotides with asterisks indicate the location of the P protein gene sequence within the sequence with GenBank accession no. AF212302). The P protein is encoded by a faithful transcript of the viral genomic RNA from an opening reading frame beginning at nucleotide 106 of the mRNA. The RNA editing site is indicated by the vertical arrow. The addition of a nontemplated G nucleotide at the RNA editing site (nucleotide 1325) allows access to a different reading frame (–1 relative to P). The V protein contains the amino-terminal domain of the P protein (horizontal lines) joined to the cysteine-rich domain that is unique to the V protein (diagonal lines). The addition of two nontemplated G nucleotides at the RNA editing site produces the mRNA for the W protein in which the amino-terminal domain of P is joined to carboxyl-terminal domain unique for W (diagonal lines). The C protein (gray box) is expressed from an opening reading frame (ORF) that begins at nucleotide 128 (or 131) and overlaps P in the +1 frame.

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FIGURE 3

Schematic representation of the coding strategy found in the P protein gene of NiV. The predicted P protein mRNA is 2,704 nucleotides in length (nucleotides with asterisks indicate the location of the P protein gene sequence within the sequence with GenBank accession no. AF212302). The P protein is encoded by a faithful transcript of the viral genomic RNA from an opening reading frame beginning at nucleotide 106 of the mRNA. The RNA editing site is indicated by the vertical arrow. The addition of a nontemplated G nucleotide at the RNA editing site (nucleotide 1325) allows access to a different reading frame (–1 relative to P). The V protein contains the amino-terminal domain of the P protein (horizontal lines) joined to the cysteine-rich domain that is unique to the V protein (diagonal lines). The addition of two nontemplated G nucleotides at the RNA editing site produces the mRNA for the W protein in which the amino-terminal domain of P is joined to carboxyl-terminal domain unique for W (diagonal lines). The C protein (gray box) is expressed from an opening reading frame (ORF) that begins at nucleotide 128 (or 131) and overlaps P in the +1 frame.

106. Wang,L.-F.,, M.Yu,, E.Hansson,, L.I. Pritchard,, B.Shiell,, W.P. Michalski, and, B.T. Eaton.2000.The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae.J. Virol.74:9972–9979.